Modifying Fraction Extracted From Sesewanua (Clerodendrum Fragrans Wild) Leaves in Snedds Preparations: Characterization and Bioavailability Test

Abstract

Objective: This study aimed to determine the effect of compound modification using acyl chloride derivatives on n-hexane: ethyl acetate fraction of sesewanua leaves, focusing on the characteristics and pharmacokinetics profile in Self-Nano-emulsifying Drug Delivery System (SNEDDS) preparations. Methods: A quasi-experimental method was used with six SNEDDS formulas, namely F0 (without active substance), F1 (acetyl chloride fraction), F2 (propanoyl chloride fraction), F3 (butyryl chloride fraction), and F4 (pentanoyl chloride fraction) and F5 (piperine compound). The fractions were subjected to characterization tests, including particle size, polydispersity index, and zeta potential as well as determination of pharmacokinetics profile using the modified crane and Wilson method. Results: The results showed that the characterization tests of particle size using Particle Size Analyzer (PSA) for F0-F5 on gastric fluid included 15.8, 17,367, 20,367, 15.8, 28.233, and 21.533 nm. The polydispersity index values were 0.211, 0.438, 0.311, 0.383, 0.394, and 0.397, while the Zeta Potential values were-22,267,-22.2,-23.5,-24,033,-22,967, and-21.6 mV, respectively. The pharmacokinetics profile of AUC0-∞ was as follows: F0 0 μg, F1 492.83, F2 492.83, F3 245.98, F4 492.94, and F5 843.38 μg. Fraction five (F5) as a control had a higher AUC0-∞ value than compared to the fractions modified with acyl chloride derivatives. The T1/2 elimination values were F0 0 h, F1 22.5 h, F2 10.811 h, F3 35.54 h, F4 231.01 h, and F5 15.469 h. Conclusion: Based on the results, the addition of acetyl, propanoyl, butyryl, and penthanoyl chloride affected Particle Size Characterization Analysis and pharmacokinetics profile of SNEDDS preparation of n-hexane: ethyl acetate fraction. Structural modification showed the ability to alter the bioavailability of the active ingredient according to the desired therapeutic goal.